Summary

For the past two decades much research on selective photothermolysis
of port wine stain vasculature has been devoted to
optimizing laser parameters. Unfortunately, 60% of patients still
respond suboptimally to laser therapy, despite significant innovations
in treatment strategies and laser technology. Here we
present a novel treatment approach based on combining selective
photothermolysis with the administration of prothrombotic
and/or anti-fibrinolytic pharmaceutical agents, with the aim of
enhancing vaso-occlusion and post-treatment remodelling in
difficult-to-target vessels.A hypercoagulable state of blood will
instill laser-induced occlusive thrombosis in a wider array of
vessel diameters at greater dermal depths, whereby larger vascular
segments will ultimately undergo the chronic inflammatory
processes that result in blood volume reduction, and thus
lesional blanching. With thrombosis as a primary trigger for
these inflammatory processes,we have extrapolated the thresh
old damage profile that is required for clinically relevant thrombus
formation. Consequently, a recently proposed model of
thrombus organization, in which recanalization is associated
with endothelial progenitor cell-mediated neovasculogenesis, is
elaborated in the framework of lesional blanching and juxtaposed
to angiogenic reconstruction of affected dermal vasculature.
Since neovasculogenesis and angiogenesis are regulated by
the degree of vaso-occlusion and corollary drop in local oxygen
tension, both can be manipulated by the administration of procoagulant
pharmaceuticals. Lastly, in an effort to optimally balance
selective photothermolysis with pharmacokinetics and
clinical safety, the use of a gold nanoshell drug delivery system,
in which the procoagulant drugs are encapsulated by a wavelength-
modulated, gold-coated polymer matrix, is proposed.We
have termed this modality site-specific pharmaco-laser therapy.